The role of miR-34c-5p/Notch in epithelial-mesenchymal transition (EMT) in endometriosis
The role of miR-34c-5p/Notch in epithelial-mesenchymal transition (EMT) in endometriosis
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DOI：
10.1016/j.cellsig.2020.109666
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发表时间：
2020-08-01
影响因子：
4.8
通讯作者：
Yang, Qing
中科院分区：
文献类型：
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作者：
Luo, Yajuan;Wang, Dandan;Yang, Qing
子宫内膜异位症是妇科常见的良性疾病，具有恶性肿瘤的生长特点，但其发病机制尚不清楚。众所周知，微核糖核酸(MiRNAs)参与了上皮-间充质转化(EMT)，与子宫内膜异位症的发生发展有关。本研究探讨了一种特殊的miRNA miR-34c-5p在子宫内膜异位症中的作用。高通量测序(HTS)显示，在东北亚地区卵巢子宫内膜异位症患者异位内膜(ECEM)中miR-34c-5p的表达降低。伤口愈合实验和跨孔侵袭实验表明miR-34c-5p可抑制Ishikawa和End1/E6E7宫颈上皮细胞的侵袭和迁移。双荧光素酶基因报告分析显示miR-34c-5p特异性靶向Notch1 3‘非编码区，Western印迹分析显示miR-34c-5p促进E-钙粘蛋白表达，但抑制Notch1、N-钙粘蛋白和波形蛋白在Ishikawa和End1/E6E7细胞中的表达。这些结果在miR-34c-5p被击倒后发生了逆转。实时定量逆转录聚合酶链式反应(qRT-PCR)和免疫印迹分析显示，Notch1在子宫内膜异位内膜(EEM)中的表达明显低于在位内膜(EuEM)。本研究结果表明，miR-34c-5p通过靶向Notch信号通路，特别是Notch1，抑制EMT的进展和细胞的侵袭和迁移。这项研究的结果为子宫内膜异位症EMT的发展和新的潜在治疗靶点提供了独特的见解。
Endometriosis, a common benign gynecological disease, has the growth characteristics of malignant tumors, however, the pathogenesis of this disease remains unclear. It is well known that micro ribonucleic acids (miRNAs) are involved in epithelial-mesenchymal transition (EMT), associated with the development of endometriosis. This study investigated the role of a specific miRNA, miR-34c-5p, in endometriosis. High-throughput sequencing (HTS) showed that miR-34c-5p expression was reduced in ectopic endometrium (ecEM) in patients from Northeast Asia with ovarian endometriosis. A wound healing assay and a transwell invasion assay showed that miR-34c-5p inhibits the invasion and migration of Ishikawa and End1/E6E7 endocervical cells. Dual luciferase gene reporter assays revealed that miR-34c-5p specifically targets Notch1 3 'UTR, and Western blot analyses showed that miR-34c-5p promotes E-cadherin expression but inhibits Notch1, N-cadherin and vimentin expression in Ishikawa and End1/E6E7 cell lines. These results were reversed following knockdown of miR-34c-5p. Using quantitative real time reverse transcriptase polymerase chain reaction (qRT-PCR) and western blot analyses, there was a significant reduction in the expression of Notch1 in ecEM compared with eutopic endometrium (euEM). The results of this study indicate that miR-34c-5p inhibits the progression of EMT and cell invasion and migration by targeting the Notch signaling pathway, specifically, Notch1. The findings of this study provide unique insights into the development of EMT in endometriosis and novel, potential therapeutic targets